Hyperbilirubinemia and Neurodevelopmental Outcome of Very Low Birthweight Infants: Results from the LIFT Cohort

Bilirubin-related neurotoxicity is an important clinical issue in very low birthweight (VLBW) infants, and the existing literature is inconsistent.To analyze the relationship between maximal serum unconjugated bilirubin levels (SBL) and neurodevelopmental outcome at 2-year corrected age in VLBW infants.Phototherapy was initiated in all infants born before 33 weeks of gestation, according to Maisels' recommendations. Neurodevelopmental assessment at 2-year corrected age was performed in all infants that survived. SBLs collected during the first week of life were used to define three tertiles of max-SBL. The first tertile corresponded to infants with the lowest max-SBL. percentile curves of SBLs in infants with an optimal outcome). When Maisels' recommendations were applied, max SBLs were higher in 8% of infants weighing 1001–1500 g and in 15% of infants weighing less than 1001 g. Our data seems to validate Maisels' recommendations in the overall population of infants born before 33 weeks of gestation, but not in infants weighing less than 1001 g

The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT

Context: Supplementation of breast milk is difficult once infants suckle the breast and is often discontinued at end of hospitalisation and after discharge. Thus, breastfed preterm infants are exposed to an increased risk of nutritional deficit with a possible consequence on neurodevelopmental outcome. Objective: To assess the relationship between breast feeding at time of discharge, weight gain during hospitalisation and neurodevelopmental outcome. Design: Observational cohort study. Setting: Two large, independent population-based cohorts of very preterm infants: the Loire Infant Follow-up Team (LIFT) and the EPIPAGE cohorts. Patients: 2925 very preterm infants alive at discharge. Main outcome measure: Suboptimal neurodevelopmental outcome, defined as a score in the lower tercile, using Age and Stages Questionnaire at 2 years in LIFT and Kaufman Assessment Battery for Children Test at 5 years in EPIPAGE. Two propensity scores for breast feeding at discharge, one for each cohort, were used to reduce bias. Results: Breast feeding at time of discharge concerned only 278/1733 (16%) infants in LIFT and 409/2163 (19%) infants in EPIPAGE cohort. Breast feeding is significantly associated with an increased risk of losing one weight Z-score during hospitalisation (LIFT: n=1463, adjusted odd ratio (aOR)=2.51 (95% CI 1.87 to 3.36); EPIPAGE: n=1417, aOR=1.55 (95% CI 1.14 to 2.12)) and with a decreased risk for a suboptimal neurodevelopmental assessment (LIFT: n=1463, aOR=0.63 (95% CI 0.45 to 0.87); EPIPAGE: n=1441, aOR=0.65 (95% CI 0.47 to 0.89) and an increased chance of having a head circumference Z-score higher than 0.5 at 2 years in LIFT cohort (n=1276, aOR=1.43 (95% CI 1.02 to 2.02)) and at 5 years in EPIPAGE cohort (n=1412, aOR=1.47 (95% CI 1.10 to 1.95)). Conclusions: The observed better neurodevelopment in spite of suboptimal initial weight gain could be termed the 'apparent breastfeeding paradox' in very preterm infants. Regardless of the mechanisms involved, the current data provide encouragement for the use of breast feeding in preterm infants

Maternal pre-pregnancy obesity and offspring hyperactivity-inattention symptoms at 5 years in preterm and term children: a multi-cohort analysis

The objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born >/= 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m(2)). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (>/= 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.Plateforme de REcherche sur les COhortes d'enfants suivis depuis la NAIssanceMaladie Rénale Chronique - Réseau Epidémiologie et Information en Néphrologi

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 24+0 and 34+6 weeks following preterm labor (PTL) or preterm premature rupture of membranes (PPROM). Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with at least two of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the non-independence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed respectively to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (adjusted odds ratio = 0.9, 95%CI: 0.5-1.8). CONCLUSION We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born before 35 weeks of gestation after PTL or PPROM

Inpatient mother-and-child postpartum psychiatric care: factors associated with improvement in maternal mental health.

International audiencePURPOSE: This study assessed the underexplored factors associated with significant improvement in mothers' mental health during postpartum inpatient psychiatric care. METHODS: This study analyzed clinical improvement in a prospective cohort of 869 women jointly admitted with their infant to 13 psychiatric Mother-Baby Units (MBUs) in France between 2001 and 2007. Predictive variables tested were: maternal mental illness (ICD-10), sociodemographic characteristics, mental illness and childhood abuse history, acute or chronic disorder, pregnancy and birth data, characteristics and mental health of the mother's partner, and MBU characteristics. RESULTS: Two thirds of the women improved significantly by discharge. Admission for 25% was for a first acute episode very early after childbirth. Independent factors associated with marked improvement at discharge were bipolar or depressive disorder, a first acute episode or relapse of such an episode. Schizophrenia, a personality disorder, and poor social integration (as measured by occupational status) were all related to poor clinical outcomes. DISCUSSION: Most women improved significantly while under care in MBUs. Our results emphasize the importance of the type of disease but also its chronicity and the social integration when providing postpartum psychiatric care

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform

Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at = 37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (= 27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.Peer reviewe

Emotional and attention-deficit/hyperactivity disorder symptoms of preterm vs. full-term children during COVID-19 pandemic restrictions

BACKGROUND: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration of children's mental health was observed during COVID-19 pandemic restrictive measures. Our study compared emotional and attention-deficit/hyperactivity disorder (ADHD) symptoms during school closure between preterm and full-term children. METHODS: Data from two French birth cohorts-ELFE and EPIPAGE-2-were used. In 2011, infants born ≥22 weeks' gestation were recruited. Parents completed the Strengths and Difficulties Questionnaire when the children were 9 years old and experiencing school closure. Multivariate multinomial logistic regression models were used. RESULTS: Subjects included 4164 full-term and 1119 preterm children. In univariate analyses, compared to full-term children: extremely and very preterm children more frequently had abnormal and borderline ADHD scores (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.50-2.30, OR 1.42, 95% CI 1.08-1.85, respectively) and abnormal emotional scores (OR 1.86, 95% CI 1.43-2.40); moderate to late preterm children more often had abnormal ADHD scores (OR 1.33, 95% CI 1.01-1.78). The associations did not remain when previous symptoms at 5 years old were considered. CONCLUSIONS: School closure during lockdown did not appear to increase the risk of mental health problems in preterm compared to full-term children. IMPACT STATEMENT: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration in children's mental health was observed during COVID-19 pandemic restrictions. However, whether preterm children were a particularly vulnerable subgroup during school closure is unclear. In univariate analyses, extremely and very preterm children more often had abnormal and borderline ADHD symptoms and abnormal emotional symptom scores than full-term children. The associations did not remain significantly associated when previous symptoms were considered. Preterm compared to full-term children more often suffer from ADHD and emotional symptoms, but school closure during lockdown did not appear to increase this risk.Santé, perception, pratiques, relations et inégalités sociales en population générale pendant la crise COVID-1

Special Care and School Difficulties in 8-Year-Old Very Preterm Children: The Epipage Cohort Study

OBJECTIVES: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children. PATIENT AND METHODS: Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents. RESULTS: Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five. CONCLUSIONS: Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores

Perspectives in the prevention of premature birth.

Obstetric and neonatal interventions have improved the survival of preterm infants, but there has not been an equivalent reduction in long-term neurological disability. Thus, some effort must be invested in finding ways of preventing preterm birth. Numerous programmes have been promoted to address the matter of how the frequency of preterm birth could be prevented. Most interventions intended to prevent preterm labour do not have the desired effect, except for antibiotic treatment in cases of asymptomatic bacteriuria or bacterial vaginosis and progesterone administered prophylactically in high-risk women. Tocolytic drugs appear to delay delivery long enough for successful administration of corticosteroids in women in preterm labour, but without decreasing the risk of preterm birth. Some authors promote public health approaches that address all risk factors and affect the entire population of pregnant women, given that prevention programmes directed only at high-risk women have had little effect in preventing preterm births. However, the lack of progress in reducing the frequency of preterm births is also due to our limited understanding of the aetiology of preterm delivery. Although there is growing evidence that infection and neuroendocrine processes are involved, progress has remained slow. Recently, the hypothesis of a genetic predisposition to preterm delivery has been set up. Additional research exploring the pathophysiology of preterm labour is obviously needed, which will hopefully lead to the development of new therapeutic approaches